Recent developments have shown that both the threshold energy and the rate of success of defibrillation are highly dependent on the spatial characteristics of the electric field created in the cardiac muscle by the shock electrodes. Current designs of defibrillatory equipment do not emphasize the quantitative importance of this factor. However, our preliminary results indicate that defibrillation techniques can be improved by using simulation methodologies which can predict these electric fields and the spatial distributions of transmembrane potential, a basic factor in stimulation and defibrillation effectiveness. The long-term objective of this project is to increase our fundamental understanding of the mechanism by which an electrical shock stops fibrillation. Primary to the study is an investigation of the spatial distribution of transmembrane potential changes in cardiac muscle generated by the shock. We propose to utilize advanced mathematical techniques to bridge the gap between parameters which can be measured experimentally and cellular-level parameters, which allegedly decide the course of defibrillation. A second objective is to improve defibrillation techniques by designing better electrode configurations for internal and external defibrillation. We plan to perform extensive simulation studies, during which the shape, number, and locations of defibrillatory electrodes will be varied. The computer models will allow us to consider large numbers of electrode configurations from which the most promising will be chosen for animal testing. Simulations will be based on realistic heart and torso geometries, and will include periodicity determined by fiber orientation and the effects of lung, skeletal muscle, and torso conductivities. An extensive data bank containing geometrical data of experimental dogs, together with some human data, will be created. Animal experiments, during which the electric field in heart will be measured, will be performed on both open-and closed chest dogs. The modeling and experimental work will be closely intertwined so that models can guide experiments, and experimental results can modify assumptions for the models. Throughout the grant period, we will process some human data to assess the feasibility of utilizing the research results to improve the effectiveness of defibrillation.